Guo Yun-Miao, Sun Ming-Xia, Li Jing, Liu Tong-Tong, Huang Hang-Zhen, Chen Jie-Rong, Liu Wen-Sheng, Feng Qi-Sheng, Chen Li-Zhen, Bei Jin-Xin, Zeng Yi-Xin
Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China.
Oncotarget. 2015 Sep 29;6(29):27176-86. doi: 10.18632/oncotarget.4870.
Nasopharyngeal carcinoma (NPC) is a malignancy with high metastatic potential and loco-regional recurrence. The overall survival of NPC has been limited from further improvement partly due to the lack of effective biomarker for accurate prognosis prediction and precise treatments. Here, in light of the implication of CELF gene family in cancer prognosis, we selected 112 tagging single nucleotide polymorphisms (SNPs) located in six members of the family and tested their associations with the clinical outcomes in a discovery cohort of 717 NPC patients. Survival analyses under multivariate cox proportional hazards model and Kaplan-Meier curve revealed five promising SNPs, which were further validated in another independent sample of 1,520 cases. Combined analysis revealed that SNP rs3740194 in CELF2 was significantly associated with the decreased risk of death with a Hazard ratio (HR) of 0.69 (95% confidence interval [CI] = 0.58-0.82, codominant model). Moreover, rs3740194 also showed a significant association with superior metastasis-free survival (HR = 0.69, 95% CI = 0.57-0.83, codominant model). Taken together, our findings suggested that genetic variant of rs3740194 in CELF2 gene might be a valuable predictor for NPC prognosis, and potentially useful in the personalized treatment of NPC.
鼻咽癌(NPC)是一种具有高转移潜能和局部区域复发风险的恶性肿瘤。NPC的总体生存率一直难以进一步提高,部分原因是缺乏有效的生物标志物来进行准确的预后预测和精准治疗。在此,鉴于CELF基因家族在癌症预后中的作用,我们选择了位于该家族六个成员中的112个标签单核苷酸多态性(SNP),并在一个由717例NPC患者组成的发现队列中测试了它们与临床结局的关联。多变量Cox比例风险模型和Kaplan-Meier曲线下的生存分析揭示了五个有前景的SNP,这些SNP在另一个由1520例病例组成的独立样本中得到了进一步验证。综合分析显示,CELF2基因中的SNP rs3740194与死亡风险降低显著相关,风险比(HR)为0.69(95%置信区间[CI]=0.58-0.82,共显性模型)。此外,rs3740194还与无转移生存期延长显著相关(HR=0.69,95%CI=0.57-0.83,共显性模型)。综上所述,我们的研究结果表明,CELF2基因中rs3740194的基因变异可能是NPC预后的一个有价值的预测指标,并可能在NPC的个性化治疗中发挥作用。